CYP2B6*6 is associated with increased breast cancer risk |
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| Authors: | Christina Justenhoven Daniela Pentimalli Sylvia Rabstein Volker Harth Anne Lotz Beate Pesch Thomas Brüning Thilo Dörk Peter Schürmann Natalia Bogdanova Tjoung‐Won Park‐Simon Fergus J. Couch Janet E. Olson Peter A. Fasching Matthias W. Beckmann Lothar Häberle Arif Ekici Per Hall Kamilla Czene Janjun Liu Jingmei Li Christian Baisch Ute Hamann Yon‐Dschun Ko Hiltrud Brauch |
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| Affiliation: | 1. Dr. Margarete Fischer‐Bosch‐Institute of Clinical Pharmacology, University of Tübingen, Stuttgart, Germany;2. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr‐University Bochum (IPA), Bochum, Germany;3. Institute for Occupational Medicine and Maritime Medicine, University Medical Center Hamburg‐Eppendorf, Hamburg, Germany;4. Department of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany;5. Department of Radiation Oncology, Hannover Medical School, Hannover, Germany;6. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN;7. Department of Health Sciences Research, Mayo Clinic, Rochester, MN;8. Division of Hematology/Oncology, Department of Medicine, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA;9. Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich‐Alexander University Erlangen‐Nuremberg, Erlangen, Germany;10. Institute of Human Genetics, University Hospital Erlangen, Friedrich‐Alexander University Erlangen‐Nuremberg, Erlangen, Germany;11. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden;12. Human Genetics, Genome Institute of Singapore, Singapore, Singapore;13. Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany;14. Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany |
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| Abstract: | ![]()
The cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of testosterone. Functional changes in this enzyme may influence endogenous hormone exposure, which has been associated with risk of breast cancer. To assess potential associations between two functional polymorphisms CYP2B6_516_G>T (rs3745274) and CYP2B6_785_A>G (rs2279343) and breast cancer risk, we established a specific matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry assay. The GENICA breast cancer case–control study showed associations between the variant genotypes CYP2B6_516_TT and CYP2B6_785_GG and breast cancer risk with odds ratios (ORs) of 1.34 (p = 0.001) and 1.31 (p = 0.002), respectively. A similar effect was observed for carriers of the CYP2B6_516_T allele in a validation study including four independent studies from Germany, Sweden and USA. In a pooled analysis of all five studies involving 4,638 breast cancer cases and 3,594 controls of European ancestry, carriers of the CYP2B6_516_G and the CYP2B6_785_G variant had an increased breast cancer risk with ORs of 1.10 (p = 0.027) and 1.10 (p = 0.031), respectively. We conclude that the genetic variants CYP2B6_516_G and CYP2B6_785_G (designated CYP2B6*6), which are known to decrease activity of the CYP2B6 enzyme, contribute to an increased breast cancer risk. |
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| Keywords: | CYP2B6 polymorphism testosterone breast cancer risk |
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